Low-frequency stimulation of STN-DBS reduces aspiration and freezing of gait in patients with PD

Sidiropoulos, Christos; Xie, Tao; Vigil, Julie; MacCracken, Ellen; Warnke, Peter C.; Kang, Un Jung

doi:10.1212/wnl.0000000000001823

“…Xie et al reported beneficial effect of LFS on FOG and swallowing function in patients with medication refractory FOG at HFS [7]. Some wondered whether the beneficial effect of the LFS was due to the reduced energy as TEED was not adjusted [23, 25]. In a follow up study, they evaluated the effect of LFS on FOG with and without adjusting the TEED in a double-blind design and reached the same conclusion on the beneficial effect of LFS on FOG and axial symptoms regardless of the TEED adjustment [8], suggesting that it is the LFS that brought the benefit, not the reduced energy, in that study.…”

Section: Effect Of Teed On the Effect Of Lfs Versus Hfsmentioning

confidence: 99%

Effect of low versus high frequency stimulation on freezing of gait and other axial symptoms in Parkinson patients with bilateral STN DBS: a mini-review

Xie

¹

,

Padmanaban

²

,

Bloom

³

et al. 2017

Transl Neurodegener

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Some studies have shown that low frequency stimulation (LFS, most commonly 60 Hz), compared to high frequency stimulation (HFS, most commonly 130 Hz), has beneficial effects, short-term or even long-term, on improving freezing of gait (FOG) and other axial symptoms, including speech and swallowing function, in Parkinson disease (PD) patients with bilateral subthalamic nucleus deep brain stimulation (STN DBS). However, other studies failed to confirm this. It seems not clear what determines the difference in response to LFS. Differences in study design, such as presence or absence of FOG, exact LFS used (60 Hz versus 80 Hz), study size, open label versus randomized double blind assessment, retrospective versus prospective evaluation, medication On or Off state, total electric energy delivered maintained or not with the change in frequency, and the location of active contacts could all potentially affect the results. This mini-review goes over the literature with the aforementioned factors in mind, focusing on the effect of LFS versus HFS on FOG and other axial symptoms in PD with bilateral STN DBS, in an effort to extract the essential data to guide our clinical management of axial symptoms and explore the potential underlying mechanisms as well. Overall, LFS of 60 Hz seems to be consistently effective in patients with FOG at the usual HFS in regards to improving FOG, speech, swallowing function and other axial symptoms, though LFS could reduce tremor control in some patients. Whether LFS simply addresses the axial symptoms in the context of HFS or has other beneficial effects requires further studies, along with the mechanism.

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“…High-frequency DBS is highly efficacious in ameliorating appendicular symptoms in PD patients, but less effective in improving axial symptoms, especially on a long-term basis [5]. New conceptions of DBS have focused on the use of LFS or combined STN/SNr-DBS for the treatment of axial symptoms in PD patients [6,9,10]. LFS may help improve postural control as well as gait, particularly in PD patients who do not develop gaitrelated disorders after HFS [11].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that subthalamic stimulation with low frequency (STN-LFS) improves axial motor activity in some PD patients, but with short-term therapeutic efficacy. Thereafter, patients may present with increased tremor, rigidity, and bradykinesia, and the intensity of symptoms often outweighs the initial benefits of LFS therapy for FOG [6,7]. Previously, we successfully used variable frequency stimulation (VFS) of the STN to treat FOG in PD patients [8].…”

mentioning

confidence: 99%

Variable versus constant frequency deep brain stimulation in patients with advanced Parkinson’s disease: study protocol for a randomized controlled trial

Jia

¹

,

Zhang

²

,

Liang

³

et al. 2019

Preprint

0

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Background: Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) can be used to treat motor symptoms and dyskinesia in the advanced stages of Parkinson’s disease (PD). High frequency stimulation (HFS) of the STN can lead to consistent, long-term improvement of PD symptoms. However, the effects of HFS on the axial symptoms of PD, specifically freezing of gait (FOG), can be limited or cause further impairment. While this can be alleviated via relatively low frequency stimulation (LFS) in select patients, LFS does not control all motor symptoms of PD. Recently, the National Engineering Laboratory for Neuromodulation reported preliminary findings regarding an efficient way to combine the advantages of HFS and LFS to form variable frequency stimulation (VFS). However, this novel therapeutic strategy has not been formally tested in a randomized trial. Methods/Design: We propose a multicenter, double blind clinical trial involving 12 study hospitals and an established DBS team. The participants will be divided into a VFS and a constant frequency stimulation (CFS) group. The primary outcome will be changes in Stand-Walk-Sit (SWS) task scores at three months of treatment in the “medication off” condition. Secondary outcome measures include specific item scores on the Freezing of Gait Questionnaire and quality of life. The aim of this trial is to investigate the efficacy and safety of VFS compared with CFS. Discussion: This is the first randomized controlled trial to comprehensively evaluate the effectiveness and safety of VFS of the STN in patients with advanced PD. VFS may represent a new option for clinical treatment of PD in the future. Trial registration: The present protocol is registered at ClinicalTrials.gov: NCT03053726.

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“…High-frequency DBS is highly efficacious in ameliorating appendicular symptoms in PD patients, but less effective in improving axial symptoms, especially on a long-term basis [5]. New conceptions of DBS have focused on the use of LFS or combined STN/SNr-DBS for the treatment of axial symptoms in PD patients [6,9,10]. LFS may help improve postural control as well as gait, particularly in PD patients who do not develop gaitrelated disorders after HFS [11].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that subthalamic stimulation with low frequency (STN-LFS) improves axial motor activity in some PD patients, but with short-term therapeutic efficacy. Thereafter, patients may present with increased tremor, rigidity, and bradykinesia, and the intensity of symptoms often outweighs the initial benefits of LFS therapy for FOG [6,7]. The conventional HFS or LFS programming is called constant frequency stimulation (CFS), due to the fixed stimulation frequency, which is the current standard method of deep brain stimulation.…”

mentioning

confidence: 99%

Variable versus constant frequency deep brain stimulation in patients with advanced Parkinson’s disease: study protocol for a randomized controlled trial

Jia

¹

,

Zhang

²

,

Wang

³

et al. 2019

Preprint

0

View full text Add to dashboard Cite

Background: Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) can be used to treat motor symptoms and dyskinesia in the advanced stages of Parkinson’s disease (PD). High frequency stimulation (HFS) of the STN can lead to consistent, long-term improvement of PD symptoms. However, the effects of HFS on the axial symptoms of PD, specifically freezing of gait (FOG), can be limited or cause further impairment. While this can be alleviated via relatively low frequency stimulation (LFS) in select patients, LFS does not control all motor symptoms of PD. Recently, the National Engineering Laboratory for Neuromodulation reported preliminary findings regarding an efficient way to combine the advantages of HFS and LFS to form variable frequency stimulation (VFS). However, this novel therapeutic strategy has not been formally tested in a randomized trial. Methods/Design: We propose a multicenter, double blind clinical trial involving 12 study hospitals and an established DBS team. The participants will be divided into a VFS and a constant frequency stimulation (CFS) group. The primary outcome will be changes in Stand-Walk-Sit (SWS) task scores at three months of treatment in the “medication off” condition. Secondary outcome measures include specific item scores on the Freezing of Gait Questionnaire and quality of life. The aim of this trial is to investigate the efficacy and safety of VFS compared with CFS. Discussion: This is the first randomized controlled trial to comprehensively evaluate the effectiveness and safety of VFS of the STN in patients with advanced PD. VFS may represent a new option for clinical treatment of PD in the future. Trial registration: The present protocol is registered at ClinicalTrials.gov: NCT03053726.

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Low-frequency stimulation of STN-DBS reduces aspiration and freezing of gait in patients with PD

Cited by 14 publications

References 6 publications

Effect of low versus high frequency stimulation on freezing of gait and other axial symptoms in Parkinson patients with bilateral STN DBS: a mini-review

Effect of low versus high frequency stimulation on freezing of gait and other axial symptoms in Parkinson patients with bilateral STN DBS: a mini-review

Variable versus constant frequency deep brain stimulation in patients with advanced Parkinson’s disease: study protocol for a randomized controlled trial

Variable versus constant frequency deep brain stimulation in patients with advanced Parkinson’s disease: study protocol for a randomized controlled trial

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